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Gene Variant May Give Milk Drinkers Lower Diabetes Risk

    Written by: Alla Katsnelson, Ph.D | Issue # 119 | 2024

    • Studies exploring the link between milk intake and type 2 diabetes risk have shown conflicting results, but they seem to be population dependent, with a favorable effect in groups that tend to be lactose intolerant.  
    • In Hispanic or Latino people, the gene variants that control whether a person’s production of lactase, the enzyme that digests the sugar in milk, persists into adulthood are fairly evenly distributed. On average, those who are lactase-non-persistent (but not those who are lactase-persistent) showed a decreased risk in Type 2 diabetes risk. 
    • Increased milk intake in lactase-non-persistent people may boost the numbers of probiotic Bifidobacteria, which in turn may produce metabolites that protect against type 2 diabetes.  

    Drinking more milk may decrease the risk of type 2 diabetes (T2D) in people who carry a gene variant that prevents the production of lactase, the enzyme that digests the sugar in milk, in adulthood, according to a new study in Nature Metabolism [1]. The benefit appears to stem from milk’s ability to boost helpful bacteria in the gut microbiome, which may in turn increase levels of metabolites associated with a lower T2D risk. 

    Several studies have explored the link between milk intake and T2D risk [2-3]. Some found a protective association, but others didn’t, says Qibin Qi, a molecular epidemiologist studying metabolic diseases at the Albert Einstein College of Medicine in New York. A few even showed the opposite, that drinking milk increases T2D risk. “The results were controversial,” says Qi. “We really didn’t know what was going on.” 

    But he and his colleagues saw a clue: Meta-analyses showed that the effect of milk intake on T2D risk was population-dependent. Studies of Asian people tended to find a protective effect, but those of European non-Hispanic white people did not. Qi wondered whether that might track with whether the enzyme lactase, which breaks down the sugar in milk, persists into adulthood. Most people who lack the enzyme as adults struggle to digest milk. This trait is governed by two variants of a gene called LCT. The LCT variant that people carry is also population-dependent. The vast majority of East Asian people carry the lactase-non-persistent variant, whereas most non-Hispanic white European people carry the lactase-persistent variant [4]. “That led to our hypothesis that maybe these differences in association between milk intake and diabetes risk might be due to differences in these genotypes across different populations,” Qi says. 

    To test this hypothesis, he and his colleagues turned to a third group: people who identify as Hispanic or Latino. “The unique thing about this population is that the LCT genotype is quite balanced,” says Qi, with about 60% of Hispanic and Latino people carrying the lactase-non-peristent variant and 40% carrying the lactase-persistent variant. 

    The researchers investigated the link between milk intake and T2D risk in a long-term US national study called the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). They analyzed data from 12,652 participants who contributed blood DNA samples and diet information to the study. Some of those participants also contributed fecal samples. Diet was assessed with a questionnaire about overall food intake and two surveys that asked participants to recall everything they consumed over the past 24 hours. In the lactase-non-persistent group, an increase in milk intake by just one serving in the two questionnaires was associated with a 30% decrease in the risk of developing T2D. 

    The researchers validated their results by probing the diet, genotype, and microbiome of participants in another large cohort called the UK Biobank Study. In that group, the effect was smaller, with milk intake pairing with a 15% decrease in T2D risk.

    Recent studies [5] have found that high milk intake was associated with an abundance of Bifidobacteria species, which have a strong probiotic effect. Here, Qi and his colleagues found that in the lactase-non-persistent participants (but not lactase-persistent participants), increased milk intake was associated with an increased number of all seven species of Bifidobacteria. This increase was also associated with a generally strong metabolic profile, consisting of features such as a lower fasting glucose level and lower amounts of adipose tissue. The researchers then examined the link between milk intake and metabolites in participants’ blood samples. In lactase-non-persistent participants, metabolites linked to a lower risk of T2D were present in higher numbers. 

    “One potential mechanism is that milk influences gut microbiota, and the gut microbiota may influence these metabolites,” Qi says. Certain species of gut bacteria, such as Bifidobacteria, may produce metabolites that the body itself doesn’t produce. In people who don’t generally consume much dairy—for example, because they struggle to digest it—that positive effect on Bifidobacteria levels may be stronger, which could explain why the effect of increased milk intake is higher. 

    Other explanations—for example, socioeconomic differences between different populations and differences in milk consumption—could be at play too, he says. 

    But a conundrum is that people who are lactase nonpersistent often have difficulty drinking more milk. “That’s the next question we really want to address,” Qi says. Some studies hint that people who don’t produce lactase could still drink milk if they introduce it very gradually. Doing so, perhaps accompanied by a probiotic containing Bifidobacteria, could potentially increase the numbers of those bacteria in the gut and thus enable lactose digestion. 

    “I don’t yet know how we will do that study,” says Qi. “We still need some detailed study designs for how to really help people to become lactose tolerant.” 

    References

    1. Luo K, Chen GC, Zhang Y, Moon JY, Xing J, Peters BA, Usyk M, Wang Z, Hu G, Li J, Selvin E, Rebholz CM, Wang T, Isasi CR, Yu B, Knight R, Boerwinkle E, Burk RD, Kaplan RC, Qi Q. Variant of the lactase LCT gene explains association between milk intake and incident type 2 diabetes. Nat Metab. 2024 Jan;6(1):169-186.
    2. Gijsbers L, Ding EL, Malik VS, de Goede J, Geleijnse JM, Soedamah-Muthu SS. Consumption of dairy foods and diabetes incidence: a dose-response meta-analysis of observational studies. Am J Clin Nutr. 2016 April;103(4):1111-24. 
    3. Alvarez-Bueno C, Cavero-Redondo I, Martinez-Vizcaino V, Sotos-Prieto M, Ruiz JR, Gil A. Effects of milk and dairy product consumption on type 2 diabetes: Overview of systematic reviews and meta-analyses. Adv Nutr. 2019 May;10(suppl_2):S154-S163. 
    4. Storhaug CL, Fosse SK, Fadnes LT. Country, regional, and global estimates for lactose malabsorption in adults: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017 Oct;2(10):738-746.
    5. Kitaoka M. Bifidobacterial enzymes involved in the metabolism of human milk oligosaccharides. Adv Nutr. 2012 May;3(3):422S-9S.